Systemic lupus erythematosus (SLE) may be induced by drugs much more frequently than is presently realized. At present nearly all the recognized cases of drug-induced SLE are due to a few drugs, including: hydralazine, procainamide, phenytoin, isoniazid, and chlorpromazine. We have shown that each of the above drugs interacts noncovalently with DNA. Further, hydralazine reacts covalently with thymidine and DNA. We plan to test the intercalative binding of these drugs by complexing them to phiX174 RF DNA. The angles of unwinding of the superhelical structure of this DNA by each of these drugs will be measured once intercalation has been established and binding isotherms have been determined. Noncovalent interaction of these drugs with chromatin and chromatin fractions will be tested. Studies of covalent reactions of hydralazine and isoniazid with DNA and chromatin will include isolation and analysis of product. The antigenicity and immunogenicity of the above noncovalent and covalent products will then be studied.